Abstract: Heart disease is the leading cause of death in the United States for both men and women. Nearly 50% of all cardiovascular deaths result from coronary artery disease. Occlusion of the left coronary artery leads to ischemia, infarction, necrosis of the affected myocardial tissue followed by scar formation and loss of function. Although myocytes in the surviving myocardium undergo hypertrophy and cell division occurs in the border area of the dead tissue, myocardial infarcts do not regenerate and eventually result in the death of the individual. Numerous attempts have been made to repair damaged myocardium in animal models and in humans. Bone marrow stem cells (BMSC) retain the ability throughout adult life to self-renew and differentiate into cells of all blood lineages. These adult BMSC have recently been shown to have the capacity to differentiate into multiple specific cell types in tissues other than bone marrow. Our research is focused on the capacity of BMSC to form new cardiac myocytes and coronary vessels following an induced myocardial infarct in adult mice. In this paper we will review the data we have previously published from studies on the regenerative capacity of BMSC in acute ischemic myocardial injury. In one experiment donor BMSC were injected directly into the healthy myocardium adjacent to the injured area of the left ventricle. In the second experiment, mice were treated with cytokines to mobilize their BMSC into the circulation on the theory that the stem cells would traffic to the myocardial infarct. In both experimental protocols, the BMSC gave rise to new cardiac myocytes and coronary blood vessels. This BMSC-derived myocardial regeneration resulted in improved cardiac function and survival.